Alternative models for influenza vaccine R&D financing

Transcription

1 Alternative models for influenza vaccine R&D financing Third WHO consultation on Global Action Plan on Influenza Vaccines (GAPIII) Nov John-Arne Røttingen, interim CEO of CEPI

2 Influenza the need for vaccines Influenza vaccines are pivotal for both prevention of seasonal epidemics and for pandemic preparedness Importance of influenza vaccines applies equally across High Income Country (HIC) and Low and Middle Income Country (LMIC) regions However: Limited efficacy of seasonal vaccines (antigenic drift and shift; limited crossprotection across virus subtypes; short duration of immunity) Improved, yet constrained manufacturing capacity and time to scale-up for pandemic vaccines Rapid response manufacturing platforms are limited (egg-based, cell-based, recombinant vaccine technologies) Maintaining production capacity is expensive Lacking a universal influenza vaccine that provides long-lasting immunity against a broad spectrum of divergent influenza viruses

3 Influenza vaccines a large market Traditionally a commercially rather unattractive global enterprise due to low profit margins and barriers to entry Today: A stable market of ~ USD 4 billion (in annual sales) for seasonal vaccines A global vaccine production capacity of ~ 1.5 billion seasonal and ~6.4 billion pandemic doses ~ 100 influenza vaccine candidates in the pipeline Faster response capabilities due to manufacturing platform technology improvements (e.g. cell-based vaccines, antigen-sparing adjuvanted vaccines, recombinant vaccines) Ongoing sharing of influenza viruses and data Driving factors/initiatives: Industry-driven investment initiatives / partnerships Global Action Plan for Influenza Vaccines BARDA Pandemic Influenza Strategy Pandemic Influenza Preparedness Framework Pandemic Influenza Vaccine procurement schemes (e.g. EU Joint Procurement Agreement)

4 Current R&D financing and incentive mechanisms Discovery Preclinic. Phase I Phase II Phase III Licensure Mfg Delivery Push mechanisms Pull mechanisms E X A M P L E S Direct investments and acquisitions (seasonal, pandemic) (Industry) Advanced Development Partnerships (seasonal, pandemic) (BARDA, Industry) Capability transfer to LMICs (pandemic) (BARDA, Industry) Idle capacity sustainment (pandemic) (BARDA) GISRS vaccine virus selection (seasonal) (WHO) Stockpiles (pandemic) (BARDA) Advance Purchase Commitments (pandemic) (Governments) Joint Vaccine Procurement (pandemic) (EU)

5 Challenges with current R&D financing mechanisms Significant costs and risks in influenza vaccine development A lengthy and costly business of failure: over a decade and at least USD 1 billion to bring new products to launch with 5% chance of success at start Particular technical and regulatory challenges with novel-antigen, novel-platform, broad spectrum use vaccines Insufficient virus data sharing due to competition and disincentives for collaboration in the market of seasonal vaccines Misalignment of R&D incentives between a stable market of seasonal vaccines and an uncertain market for pandemic or universal vaccines challenge for market transition Rapid R&D response capabilities nurtured by too limited public funding (almost only BARDA) Manufacturing capacity patchy and costly for pandemic vaccines market failure (in particular for LMICs) Global access to influenza vaccines in the event of a pandemic is not guaranteed

6 Why are alternative R&D financing mechanisms needed? Due to Market failure (Pandemic vaccines) Market transition failure (New seasonal or Universal vaccines) To mobilize new resources and complement the current menu of reward mechanisms to incentivize influenza vaccine R&D To incentivize a smooth and sustainable shift of R&D efforts and knowhow from a relatively stable market of current seasonal vaccines to a more uncertain market of pandemic and novel universal vaccines, through: better risk and benefit sharing arrangements between industry and society reduced supply shortages and more equitable access provisos to underserved populations Improved technical and institutional platforms to improve speed of R&D response More collaborative and transparent partnership models for novel R&D and data sharing

7 What kind of R&D financing mechanisms are needed? New methods and sources of financing (= resource mobilization mechanisms) Offering incentives to encourage shift from focus of current market (= reward mechanisms) Through tailored partnership models with a common mission based on collaborative principles of risk and benefit sharing

8 What kind of R&D financing mechanisms are needed?

9 Resource mobilization examples from global health R&D beyond just vaccines SOURCES Governments / citizens / philanthropists Private sector ODA and national health R&D budgets Earmarked taxes and fees / e.g. airline ticket tax Various consumer voluntary contributions Private giving campaigns INDICATIVE EXAMPLES Pooled funding through management and coordination intermediaries e.g. PDPs, Pledge / guarantee backed debt/equity financing / e.g. IFFIm, GHIF Retained earnings / re-invested business revenue In-kind contributions / e.g. in PDPs, in IMI, in GHIT Fund, etc. Various debt/equity financing instruments

10 Reward mechanisms examples from global health R&D beyond just vaccines PAYMENTS Direct INDICATIVE EXAMPLES Grants Various end-product and milestone prizes Procurement Risk-sharing loans Venture capital Private sector patent buy-outs / buy-backs Risk/cost sharing through PDPs Incubators / accelerators Advance Market Commitments Indirect Liability protection Volume guarantees R&D tax credits and relief programmes Regulatory and legislation Tiered pricing schemes Patent pools

11 Lessons from CEWG? (Consultative Expert Working Group on Research and Development: Financing and Coordination) Balancing innovation and access by complying with following criteria: Delinkage of the price of the final product from the cost of the R&D Utilize collaborative approaches, especially open knowledge innovation approaches Utilize licensing approaches that secure access to final products Continuously strive to mobilize new sources of financing Foster effective and efficient coordination mechanisms amongst existing organizations/initiatives Strengthen capacity for R&D and production, including through technology transfer, in LMICs

12 What could such mechanisms look like? CEPI is one ambitious new publicprivate partnership between governments, industry, philanthropy, academia, civil society, and other global health stakeholders. Responding to the calls of several highprofile panel and expert reports to address critical R&D gaps for pandemic preparedness and global health security, CEPI will proactively develop new vaccines for priority emerging infectious diseases (EIDs) to stop future outbreaks before they become public health emergencies. 12

13 Ebola: Timing of phase III trials 23 Oct WHO High level meeting Guinea working group formed 9 months 9 months 6 months 1 Sept Extension to Sierra Leone 90 rings 11 Aug 5 Nov 5 Feb 23 Mar 7 Aug WHO Ethics Report Ring design decided Vaccine choice Vaccination initiated Last randomized ring vaccinated Sept WHO Consultation on Ebola Vaccines Dec-Jan Protocols / Financing 31 Jul Preliminary results 1 Jan Start stability study 20 Jul Interim analysis

14 Coalition for Epidemic Preparedness Innovations CEPI January November 2016 High Level Meeting Davos 21 January Task Team Meeting Meeting, Oslo 6-7 April Task Team Teleconferences Leadership Group Meeting Washington DC 17 May Interim CEO appointed Interim board constituted Business Plan presented to stakeholders Core Group and Leadership Group Teleconferences First CEPI interim board meeting London, 31 August CEPI soft launch Media coverage G7 Health ministers side event, Kobe, 10 September UNGA side event on health emergencies, NY, 19 September

15 CEPI - Vision Vaccines contributing to preventing outbreaks from becoming humanitarian crises

16 CEPI - Mission To prioritize, stimulate, finance and co-ordinate vaccine development against emerging infections with epidemic potential, especially in cases where market incentives alone do not achieve this

17 Timely vaccine development objectives for efficient global R&D preparedness Live attenuated virus vaccines Whole killed virus vaccines (other forms of proteinparticulate vaccines) VLP (Virus-Like-Particle) DNA/RNA vaccines vaccines, other non-living Self-Amplifyingtechnologies (e.g.liposomes) Material (SAM )

18 CEPI s Gap-Filling Role CEPI role as a facilitator Significant focus by others CEPI role as a funder Significant focus by others Phase Current Stakeholders 1 Discovery Academia Governments WT/NIH GLOPID-R Industry Regulators Biotech IMI / EC 2 Development/Licensure Industry National Governments Regulators Bill and Melinda Gates Foundation BARDA/DTRA etc. WHO Biotech PDPs IMI / EC 3 Manufacturing Industry BARDA CMOs Regulators National Governments WHO GHIF 4 Delivery/Stockpiling GAVI UNICEF PAHO National Governments WHO Industry Pandemic Emergency Facility (World Bank) WHO Contingency Fund Adhering to equitable access principles of affordable pricing and availability of vaccines by priority populations in emergencies Securing industry participation through predictable pathways and risk/benefit sharing arrangements and handling of liability through indemnification Supporting data sharing and sample sharing mechanisms, and long-term development of regional capabilities for epidemic vaccine preparedness 18

19 Organizational Setup: Startup Phase Founding Partners include the Gates Foundation, Wellcome Trust, Department of Biotechnology of India, Government of Norway, and World Economic Forum Independent legal entity, existing as an international non-profit association under Norwegian law Interim Secretariat is hosted by the Norwegian Institute of Public Health under a service agreement Flexible arrangement, can transition into other institutional and governance arrangements Decisions about its permanent organizational structure and governance made by the CEPI Interim Board during the interim phase SAC advises on scientific matters and JCG coordinates CEPI s activities with other stakeholders 19

20 CEPI s Funding Needs Preliminary costmodeling estimates 5-year costs for advancement of 10 WHO Blueprint EID vaccine candidates to the end of clinical phase II development at between US$600M and US$3.7B, depending on the complexity of the technology used, pilot manufacturing requirements and other manufacturing cost variants, and stockpiling needs. CEPI is seeking multi-year donor contributions to an initial investment pool of US$1B ( ) to advance late-stage development of 4 to 6 vaccine candidates against 2 to 3 priority EIDs to the end of clinical phase II development, and save countless lives and billions of dollars. 20

21 CEPI Financing Model CEPI will use a multi-source financing model to satisfy its core resource needs. Four financing principles 1. Broad-based 2. Long term, predictable 3. Complementary and new financial resources 4. Fit-for-purpose funding

22 CEPI Partnership Models VACCINE INDUSTRY Aligned contributions from industry and other R&D partners, including staff support, access to IP, and use of vaccine production lines that will significantly reduce CEPI s overall costs and production timelines. INTERNATIONAL INVESTORS Direct investor contributions through multi-year grants and innovative financing mechanisms like IFFIm, which will complement indirect support through alignment on domestic R&D investments and regulatory policies. DEVELOPING COUNTRIES CEPI s Solidarity Fund will channel tiered, equitable contributions from affected countries that will benefit from CEPI s insurance policy against future pandemics emergencies. Solidarity Fund partners will also contribute and benefit through advance coordination on clinical trial arrangements. 22

23 CEPI Investing together A risk sharing mechanism We do not know where the next outbreak will hit We do not know which pathogen it will be Resources/investments are constrained and limited In finance terms we need to: Collateralize and securitize investments Share risks National health systems are risk sharing mechanisms (i.e. UHC) For global health security we need global risk sharing mechanisms across countries to Prevent, detect and respond to outbreaks Invest in R&D for biomedical countermeasures Pay as you go will be costly and will not solve the problem!

24 Conclusions Increasing risk of pandemic influenza outbreaks carrying significant public health and economic burden Influenza vaccines are pivotal for both prevention of seasonal epidemics and of pandemic preparedness Need for new influenza vaccines: limited efficacy of seasonal vaccines, constrained manufacturing capacity and time to scale-up for pandemic vaccines, and lack of a universal influenza vaccine A stable market for seasonal vaccines creates barriers to developing novel pandemic and universal vaccines, which are characterized by highly uncertain markets Public funding is too limited: WHO, BARDA, EU pioneers in push/pull incentives for better influenza vaccine preparedness A balance of access and innovation principles is key for fostering societally and globally acceptable R&D financing mechanisms, as demonstrated by CEWG CEPI is an example of a global institutional mechanism example with responsibility to incentivize vaccine R&D preparedness through new funding sources and flexible use of incentives but adhering to global access and risk/benefit sharing principles